The assay of clinically important molecules at low concentration is most often accomplished by immunoassay, but limitations result in some molecules of biomedical interest having no reliable measure. We have developed breakthrough technology that overcomes this problem with broad application. We provide an innovation of the instrumental technique, isotachophoresis (ITP), that allows quantitative introduction of specimen to capillary electrophoresis (CE) coupled with electrospray ionization time-of-flight mass spectrometry (TOFMS), a rapid, sensitive and specific detector. In Phase I we will target two families of molecules, catecholamines and angiotensins, important in the evaluation of hypertension and apply this approach to achieve more specific or sensitive assays. We will define conditions needed to reduce ITP-CE-TOFMS to routine assay, comparing our results to the best assays available. For analytes where no assay exists we will perform standard evaluations. The prototype ITP instrument has no interface with TOFMS, hence, in Phase I we will build a second ITP-CE system interfaced to TOFMS and dedicated to the studies proposed here and later as a core instrument in a reference laboratory. In Phase II we will acquire a dedicated TOFMS to finalize a stand-alone operation. We will demonstrate the clinical utility of our method in the diagnosis of well-characterized hypertensive patients. We will acquire other components and staff to support a fee-for-service lab, intended to achieve financial independence by filling a niche market: providing excellent assays where none exist. PROPOSED COMMERCIAL APPLICATION: The technique is well suited for the measurement of small peptides, small amines and small biological acids. Many of these are important in medical diagnosis and research but assays do not exist for them or are of poor quality. Marketing assays on a fee basis underlies the operation of several reference laboratories.